The kidneys are organs that perform several functions as one of the important eliminatory organs. They work not only as eliminatory organs that regulate the body's fluid volume, excrete wastes and adjust electrolyte content, but as endocrine organs that secrete hormones such as erythropoietin (for red blood cell production) and rennin (for blood pressure control) and control the metabolism of vitamin D3 to maintain parathyroid function and calcium metabolism. They also work as organs for metabolism that destroy a peptide hormone, reabsorb low molecular proteins, and regulate the glucose/lipid metabolism. The examples of kidney disease are nephritis, renal failure, kidney cancer, etc., and nephritis is the most typical kidney disease. In patients with continued nephritis, chronic renal failure, hypertension, or other diseases appear due to a loss of kidney function, causing complications such as damage to other organs, metabolic abnormality, or the like. The loss of kidney function goes unnoticed until 70% or more of the kidney function is gone. If renal failure remains unnoticed without an appropriate treatment, dialysis or kidney transplant is the only treatment for the patient. In South Korea, the number of patients going on dialysis is increasing by 4,000 to 5,000 each year, and the number of kidney transplant patients is also ascending. Continuous dialysis is necessary until kidney transplantation is done, resulting in a great pain or economic burden to the patient. As for kidney transplant, a lack of kidney donors causes a long wait, even with a social problem related to organ trafficking.
In case of immune-complex mediated nephritis that is found in about 70% of the patients with nephritis, antigens within/from the body bind to antibodies produced in the body to form antigen-antibody complexes, which deposit within glomerular basement membranes and mesangial cells to cause inflammation and damage on the glomeruli. Anti-glomerular basement membrane antibody nephritis induced by similar immune response is a disease that anti-glomerular basement membrane antibodies formed within the body deposit in the glomerular basement membranes to cause acute inflammation, and found in about 5% of the patients with nephritis. Contamination of urinary organs such as urinary tract, bladder, etc. with pathogenic bacteria or viruses may allow an ingress of pathogens into kidneys to induce nephritis.
The medications for nephritis include immune-suppressant drugs, anti-inflammatory drugs, hypertension/vasoactive drugs, antibiotics, and so forth. The immune-suppressant drugs reduce formation of antibodies, which triggers nephritis, to inhibit deposition of antigen-antibody complexes and anti-inflammatory drugs suppress inflammation, thereby improving nephritis symptoms. Angiotensin II antagonists used as hypertension/vasoactive drugs accelerate production of basement membranes that are vascular cell walls acting like glomerular filters, to activate the kidney functions. For infection-induced nephritis, quinolone antibiotics are used to kill pathogenic bacteria causing nephritis.
Patients with nephritis are mostly with autoimmune glomerulonephritis, which is treated primarily with immune-suppressant drugs, anti-inflammatory drugs, and hypertension/vasoactive drugs. Infection-induced pyelonephritis is treated with quinolone antibiotics. The examples of the immune-suppressant drugs for nephritis include tacrolimus, eculizumab, mycophenolate mofetil, cyclosporine A, etc. The examples of the anti-inflammatory drugs include dexamethasone, prednisolone, etc. The hypertension/vasoactive drugs for glomerulonephritis are, for example, candesartan, and rituximab and abatacept which have the antitumor activity. The medicines for pyelonephritis are levofloxacine and gatifloxacin. The patients with nephritis in other countries than Korea are mostly treated with immune-suppressant drugs, such as tacrolimus, mycophenolate mofetil, or eculizumab. In Korea, antibiotics are most commonly used medications for nephritis, and the use of immune-suppressant drugs for nephritis is increasing in recent years.
The long-term use of immune-suppressant drugs or antibiotics, however, results in adverse effects, including ulceration, edema, an increase of infection, hypertension, hepatotoxemia, and so forth, so immune-suppressant drugs and antibiotics are limited in use. Hence there is a demand for developing novel medicines for nephritis with less adverse effects than the existing medicines for nephritis and with secured safety.
For that reason, novel medicines for nephritis using natural substances have recently been developed.